Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Apr 8;9(4):e93965. doi: 10.1371/journal.pone.0093965. eCollection 2014.

Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms.

Author information

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, North Dakota, United States of America; Departments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • 2Departments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • 3Department of Nephrology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • 4Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
  • 5Department of Physiology and Functional Genomics College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • 6Departments of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, United States of America; Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

Erratum in

  • PLoS One. 2014;9(7):e103913. LiCalzi, Sergio [corrected to Li Calzi, Sergio]; Jhadao, Chandra [corrected to Jadhao, Chandra].

Abstract

We hypothesized that endothelial progenitor cells derived from individuals with diabetes would exhibit functional defects including inability to respond to hypoxia and altered paracrine/autocrine function that would impair the angiogenic potential of these cells. Circulating mononuclear cells isolated from diabetic (n = 69) and nondiabetic (n = 46) individuals were used to grow endothelial colony forming cells (ECFC), early endothelial progenitor cells (eEPCs) and isolate CD34+ cells. ECFCs and eEPCs were established from only 15% of the diabetic individuals tested thus directing our main effort toward examination of CD34+ cells. CD34+ cells were plated in basal medium to obtain cell-free conditioned medium (CM). In CM derived from CD34+ cells of diabetic individuals (diabetic-CM), the levels of stem cell factor, hepatocyte growth factor, and thrombopoietin were lower, and IL-1β and tumor necrosis factor (TNFα) levels were higher than CM derived from nondiabetic individuals (nondiabetic-CM). Hypoxia did not upregulate HIF1α in CD34+ cells of diabetic origin. Migration and proliferation of nondiabetic CD34+ cells toward diabetic-CM were lower compared to nondiabetic-CM. Attenuation of pressure-induced constriction, potentiation of bradykinin relaxation, and generation of cGMP and cAMP in arterioles were observed with nondiabetic-CM, but not with diabetic-CM. Diabetic-CM failed to induce endothelial tube formation from vascular tissue. These results suggest that diabetic subjects with microvascular complications exhibit severely limited capacity to generate ex-vivo expanded endothelial progenitor populations and that the vasoreparative dysfunction observed in diabetic CD34+ cells is due to impaired autocrine/paracrine function and reduced sensitivity to hypoxia.

PMID:
24713821
[PubMed - indexed for MEDLINE]
PMCID:
PMC3979711
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk